J. K. Van Der Korst

Food intolerance in rheumatoid arthritis. I. A double blind, controlled trial of the clinical effects of elimination of milk allergens and azo dyes.

The hypothetically negative influence of food on the clinical activity of seropositive rheumatoid arthritis was studied using two types of artificial elementary food. One diet was allergen free, the other allergen restricted, containing only lactoproteins and yellow dyes. Ninety four patients entered the study, which lasted 12 weeks. During the second four week period they were randomly assigned to one of the two artificial foods. Comparison between baseline and subsequent periods showed only subjective improvements. No differences were seen between the clinical effects of the two tested diets. Nine patients (three in the allergen restricted group, six in the allergen free group) showed favourable responses, followed by marked disease exacerbation during rechallenge. Dietary manipulation also brought about changes in objective disease activity parameters in these patients. The existence of a subgroup of patients in whom food intolerance influences the activity of rheumatoid factor seropositive rheumatoid arthritis deserves serious consideration.

Effects of total hip replacement on quality of life in patients with osteoarthritis and in patients with rheumatoid arthritis.

SummaryThe effects of total hip replacement (THR) on quality of life were investigated in 62 patients with osteoarthrosis (OA) and 35 patients with rheumatoid arthritis (RA). Patients eligible for a first hip joint replacement were enrolled consecutively and examined at home before the operation and 3, 6, and 12 months after surgery.The IRGL (Influence of Rheumatic Diseases on Health and Lifestyle), a Dutch version of the AIMS (Arthritis Impact Measurement Scales), was used to operationalize quality of life in a questionnaire.Pain and mobility scores showed significant improvement among both OA and RA patients. The general mood of the OA patients also improved significantly, but the RA group showed only a favourable tendency in this respect. The interference of OA in several areas of life almost disappeared, whereas the impact of RA was only slightly reduced. There was no discernible effect on the social dimension in either group. A single THR apparently solves the main problem of most OA patients, but only one of a number of joint problems for most RA patients. The IRGL is complex and time-consuming and contains irrelevant scales. Its multidimensional evaluation of the quality of life is more informative than a purely somatic evaluation.

BOVINE SESAMOID BONES: A CULTURE SYSTEM FOR ANATOMICALLY INTACT ARTICULAR CARTILAGE

SummaryMedial sesamoid bones from the metacarpophalangeal joints of calves were used for prolonged culture of anatomically intact articular cartilage on its natural bone support. The cartilage remained viable during culture, without signs of degeneration. After 1 wk of culture the cartilage showed an increased proteoglycan synthesis, and some minor changes in the composition of newly synthesized proteoglycans were observed. In the next 7 wk all studied parameters remained constant, except for the rate of proteoglycan synthesis, which declined between 4 and 8 wk to values just below those measured at the start of culture. Despite the fact that newly synthesized proteoglycans showed some altered biochemical properties, the composition of the total pool of proteoglycans did not change during 8 wk of culture. The significance of this phenomenon is discussed. This new in vitro model of intact articular cartilage offers a promising alternative to in vivo studies because in contrast to other in vitro models no surgical injury of the cartilage is introduced.

Determination of d-penicillamine in serum and urine of patients with rheumatoid arthritis

A chromatographic auto-analyser method is described for the determination of total D-penicillamine in biological fluids. After oxidation with performic acid, D-penicillaminic acid is separated from other ninhydrin-positive acidic amino acids by anion-exchange chromatography. Total cysteine/cystine is simultaneously determined as cysteic acid, which makes the method equally suitable for patients with cystinuria. The detection limit in serum and urine is 2 microM D-penicillamine, which is more than sufficient for clinical application. The metabolite S-methyl-D-penicillamine is oxidized by performic acid to a sulphone, which can be determined after separation by cation-exchange chromatography.

COMPOSITION OF PROTEOGLYCANS SYNTHESIZED IN DIFFERENT LAYERS OF CULTURED ANATOMICALLY INTACT ARTICULAR CARTILAGE

Calf articular cartilage was cultured anatomically intact on its natural bone-support. At day 0 and day 7, respectively, the cartilage was radiolabeled, washed and harvested in 3 successive layers parallel to the articular surface. The proteoglycans were studied after extraction by 4 M guanidine hydrochloride. In the deep layer, the endogenous proteoglycan monomers were slightly smaller, showed an increased polydispersity and the relative amount of keratan sulfate was lower. In addition, chondroitin sulfate side chains were slightly larger and the sulfation degree and proportion of 4-sulfated disaccharides was elevated. At day 0, deep layer chondrocytes incorporated about twice as much [35S]-sulfate into glycosaminoglycans as did superficial chondrocytes. The newly synthesized proteoglycan monomers were the same in all layers with respect to size, dispersity, relative amount of keratan sulfate and size of chondroitin sulfate side chains. The sulfation-pattern, however, changed with depth in the same way as noted in the endogenous proteoglycan population. Small endogenous proteoglycan was present in all layers, but its synthesis was only prominent in the upper layer and decreased with depth. After 7 days culture, the [35S]-sulfate incorporation had increased in the upper half of the cartilage. There was a strong increment in the proportion of 6-sulfated disaccharides of newly synthesized glycosaminoglycan in all layers. The synthesis of small proteoglycan was markedly reduced, especially in the upper layer.

Bone metabolism in rheumatoid arthritis compared with postmenopausal osteoporosis.

Calcium and bone metabolism in 29 rheumatoid arthritis (RA) patients were compared with those in 27 postmenopausal osteoporotic patients. Signs of vitamin D deficiency were found in 20 RA patients, including 12 who took recommended amounts of vitamin D in their diets and were exposed to sufficient sunlight, and in none of the osteoporotic patients. There were no signs of malabsorption. In six out of 15 patients we found increased liver enzyme activity, which may have a role in vitamin D metabolism. We propose the influence of non-steroidal anti-inflammatory drugs (NSAIDs) on vitamin D metabolism in the liver as a possible explanation.

Extra-articular manifestations of rheumatoid arthritis: risk factors for serious gastrointestinal events.

OBJECTIVES--Serious upper gastrointestinal events are an important threat to patients with arthritis who are treated with non-steroidal anti-inflammatory drugs (NSAIDs). In this study risk factors for serious upper gastrointestinal events are identified in patients with possible or definite rheumatoid arthritis (RA). METHODS--A retrospective analysis of factors that might contribute to the risk of serious upper gastrointestinal events was performed in a cohort of 2315 consecutive patients with possible or definite RA. The relative influences of disease severity, drug treatment, particularly with corticosteroids, and history of peptic ulceration were analysed with a conditional logistic regression model for the 106 patients with serious upper gastrointestinal intestinal events and for an equal number of control patients who were matched for age, gender, number of criteria for RA, and disease duration. RESULTS--The incidence rate for serious upper gastrointestinal events was 4.0/1000 patients in each year. The study reconfirmed that age over 60 years, history of peptic ulceration, and use of corticosteroids are risk factors. The presence of extra-articular manifestations of RA was associated with a two to 11-fold increase in the risk for serious upper gastrointestinal events. This risk was independent of the use of corticosteroids. CONCLUSION--Disease severity, in particular the presence of extra-articular features, may be an important factor in the pathogenesis of upper gastrointestinal ulceration in patients with RA who are treated with NSAIDs.

Food intolerance in rheumatoid arthritis. II. Clinical and histological aspects.

Six patients with rheumatoid factor positive rheumatoid arthritis who had shown a marked symptomatic improvement during four weeks of hypoallergic, artificial diet were studied in greater detail. Placebo controlled rechallenges showed intolerance for specific foodstuffs in four patients. In three of these patients biopsies of both the synovial membrane and of the proximal small intestine were carried out before and during allergen free feeding. In two patients, both with raised serum IgE concentrations and specific IgE antibodies to certain foods, a marked reduction of mast cells in the synovial membrane and proximal small intestine was demonstrated. Although the number of food intolerant patients with RA remains limited and markers of allergic activity are scanty, our observations suggest an underlying immunoallergological mechanism.

Components of health: an analysis in rheumatoid arthritis using quality of life questionnaires and clinical and laboratory variables.

OBJECTIVE--To gain insight into the overlap between additional information supplied by recently developed health status instruments for rheumatoid arthritis (RA) and traditional clinical and laboratory tests. METHODS--A cross sectional study of 282 outpatients with RA was made. From each patient, variables of clinical and laboratory measurements were obtained and the modified health assessment questionnaire (MHAQ) and a Dutch quality of life questionnaire, the IRGL, were completed. These variables were analysed for their interrelationship. RESULTS--Clinical and laboratory variables correlated significantly with the scales of the physical dimension and the disease impact scale of the IRGL. Their significant correlations with the IRGL psychological scales were weak. There were no significant correlations between any of the traditional variables and the IRGL social scales. Factor analysis yielded five factors: functionality, pain, depressive mood, social support, and laboratory. The laboratory factor is a measure of the disease process. The other four factors provide a health model. CONCLUSION--The results suggest that the IRGL questionnaire that was studied covers a complete health model that incorporates aspects of health that are not measured by clinical and laboratory tests. A simple questionnaire for the psychological and social dimension of health status, however, would probably be more cost effective and easier to use in clinical practice.

Rheumatoid arthritis, food, and allergy

One of the most promising lines of research on the etiology and pathogenesis of rheumatoid arthritis (RA) is its association with the genetically determined MHC class II antigens. The function of these macromolecules, presentation of antigens to the T-helper cells, supports the possibility that external antigens influence RA. We review available literature concerning the relationship between RA and food. Circumstantial evidence suggests that some foods or food components might influence subgroups of RA patients, although many of the publications on this subset do not meet acceptable standards of modern medical research.